Neural circuits underlying the pathophysiology of mood disorders

Joseph L. Price, Wayne C. Drevets
2012 Trends in Cognitive Sciences  
Although mood disorders constitute leading causes of disability, until recently little was known about their pathogenesis. The delineation of anatomical networks that support emotional behavior (mainly derived from animal studies) and the development of neuroimaging technologies that allow in vivo characterization of anatomy, physiology, and neurochemistry in human subjects with mood disorders have enabled significant advances towards elucidating the pathophysiology of major depressive disorder
more » ... (MDD) and bipolar disorder (BD). In this review, we integrate insights from human and animal studies, which collectively suggest that MDD and BD involve dysfunction within an extended network including the medial prefrontal cortex and anatomically-related limbic, striatal, thalamic and basal forebrain structures. Animal and human studies of mood disorders Major depressive disorder (MDD) and bipolar disorder (BD) constitute the first and fifth leading causes of years lived with disability, respectively [1]. Yet, until recently, little was known about their pathogenesis, as these conditions are not associated with gross brain pathology or clear animal models for spontaneous recurrent mood episodes. The development of neuroimaging technologies that allow in vivo characterization of anatomy, physiology, and neurochemistry in human subjects with mood disorders has enabled significant advances toward elucidating their pathophysiology. Crucially, the interpretation of the abnormalities found using these technologies has depended upon by the concomitant delineation of anatomical networks that support emotional behavior. Early studies identified the amygdala, hippocampus, and other parts of what was termed the 'limbic' system as central parts of the emotional brain. Beginning in the 1970s and 1980s and continuing through the last 15 years, neuroanatomical techniques based on axonal transport have been applied extensively to the limbic system and prefrontal cortex of monkeys. With these methods, a system has been described that links the medial prefrontal cortex (mPFC) and a few related cortical areas to the amygdala, the ventral striatum and pallidum, the medial thalamus, the hypothalamus, and the periaqueductal gray and other parts of the brainstem. A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material, indicates that this system is centrally involved in mood disorders. In this review we discuss the neuroanatomy of the neural circuits implicated in mood disorders, synthesizing findings from studies of non-human primates and observations in humans, largely taken from clinical studies. The results of these studies, conducted using neuroimaging, lesion analysis, and post mortem methodologies, support models in which the pathophysiology of depression involves dysfunction in an extended network involving the mPFC and anatomically-related limbic, striatal, thalamic and basal forebrain structures. The abnormalities of structure and function evident within the extended 'visceromotor' network putatively impair this network's roles in cognitive processes such as reward learning and autobiographical memory, and may dysregulate visceral, behavioral and cognitive responses to emotional stimuli and stress [2], potentially accounting for the disturbances manifest within these domains in mood disorders. Cognitive and emotional disturbances in MDD and BD The clinical phenomenology of major depression implicates brain systems involved in the regulation of mood, anxiety, fear (e.g., panic attacks, phobias and post-traumatic stress syndromes commonly occur co-morbidly with depression), reward processing, attention, motivation, stress responses, social interaction, and neurovegetative function (i.e., sleep, appetite, energy, weight, libido) [1]. In BD, episodes of depression occur alternately with manic or hypomanic episodes, during which mood can become euphoric and labile, motivated and reward seeking behavior increases, and psychomotor activity and self-esteem become elevated.
doi:10.1016/j.tics.2011.12.011 pmid:22197477 fatcat:btjyfiyfyrbq3plck75rgnkzwu